Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA217507 | ENA |
REPOSITORIES: ENA
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Project description:When using cell lines to study cancer, phenotypic similarity to the original tumor is paramount. Yet, little has been done to characterize how closely Merkel cell carcinoma (MCC) cell lines model native tumors. To determine their similarity to MCC tumor samples, we characterized MCC cell lines via gene expression microarrays. Using whole transcriptome gene expression signatures and a computational bioinformatic approach, we identified significant differences between variant cell lines (UISO, MCC13, and MCC26) and fresh frozen MCC tumors. Conversely, the classic WaGa and Mkl-1 cell lines more closely represented the global transcriptome of MCC tumors. When compared to publicly available cancer lines, WaGa and Mkl-1 cells were similar to other neuroendocrine tumors, but the variant cell lines were not. WaGa and Mkl-1 cells grown as xenografts in mice had histological and immunophenotypical features consistent with MCC, while UISO xenograft tumors were atypical for MCC. Spectral karyotyping and short tandem repeat analysis of the UISO cells matched the original cell line's description, ruling out contamination. Our results validate the use of transcriptome analysis to assess the cancer cell line representativeness and indicate that UISO, MCC13, and MCC26 cell lines are not representative of MCC tumors, whereas WaGa and Mkl-1 more closely model MCC. RNA was extracted from MCC cell lines and MCC and SCLC tumor samples and hybridized to Affymetrix microarrays for transcriptome profiling.
2014-12-23 | E-GEOD-50451 | biostudies-arrayexpress
Project description:Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine tumor with high mortality rates. Merkel cell polyomavirus (MCPyV), identified in the majority of MCC, may drive tumorigenesis via viral T antigens. However, mechanisms underlying pathogenesis in MCPyV-negative MCC remain poorly understood. To nominate genes contributing to pathogenesis of MCPyV-negative MCC, we performed DNA microarray analysis on 30 MCCs. MCPyV status of MCCs was determined by PCR for viral DNA and RNA. 1593 probe-sets were differentially expressed between MCPyV-negative and -positive MCC, with significant differential expression defined as at least 2-fold change in either direction and p-value of ≤ 0.05. MCPyV-negative tumors showed decreased RB1 expression, whereas MCPyV-positive tumors were enriched for immune response genes. Validation studies included immunohistochemistry demonstration of decreased RB protein expression in MCPyV-negative tumors and increased peritumoral CD8+ T lymphocytes surrounding MCPyV-positive tumors. In conclusion, our data suggest that loss of RB1 expression may play an important role in tumorigenesis of MCPyV-negative MCC. Functional and clinical validation studies are needed to determine whether this tumor suppressor pathway represents an avenue for targeted therapy. We used microarrays to characterize global gene expression patterns related to Merkel cell polyomavirus status in Merkel cell carcinoma. Furthermore, we compared Merkel cell carcinoma to less aggressive primary cutaneous carcinomas. We utilized flash-frozen tumor tissue from primary Merkel cell carcinomas, metastatic Merkel cell carcinomas, primary cutaneous squamous cell carcinomas, and basal cell carcinomas. Merkel cell carcinoma cell lines, which represent a pure population of tumor cells, were also included. Merkel cell polyomavirus status was determined at the DNA and RNA level using multiple primers for viral T-antigen and capsid protein sequences. This Series represents two analyses - one with new Samples normalized together, and another with some of the new Samples re-normalized with Samples previously submitted under Series GSE13355. The latter group contain 'renormalized' in the titles.
2012-10-18 | E-GEOD-39612 | biostudies-arrayexpress
Project description:MicroRNAs have been implicated in various skin cancers, including melanoma, squamous cell carcinoma, and basal cell carcinoma; however, the expression of microRNAs and their role in Merkel cell carcinoma (MCC) have yet to be explored in depth. To identify microRNAs specific to MCC (MCC-miRs), next-generation sequencing (NGS) of small RNA libraries was performed on different tissue samples including MCCs, other cutaneous tumors, and normal skin. Comparison of the profiles identified several microRNAs upregulated and downregulated in MCC. For validation, their expression was measured via qRT-PCR in a larger group of MCC and in a comparison group of non-MCC cutaneous tumors and normal skin. Eight microRNAs were upregulated in MCC: miR-502-3p, miR-9, miR-7, miR-340, miR-182, miR-190b, miR-873, and miR-183. Three microRNAs were downregulated: miR-3170, miR-125b, and miR-374c. Many of these MCC-miRs, with the miR-183/182/96a cistron in particular, have connections to tumorigenic pathways implicated in MCC pathogenesis. In situ hybridization confirmed that the highly expressed MCC-miR, miR-182, is localized within tumor cells. Furthermore, NGS and qRT-PCR reveals that several of these MCC-miRs are highly expressed in the patient-derived MCC cell line, MS-1. These data indicate that we have identified a set of MCC-miRs with high implications for MCC research. To identify microRNAs specific to Merkel cell carcinoma (MCC) next-generation sequencing (NGS) of small RNA libraries was performed on different tissue samples including MCCs, other cutaneous tumors, and normal skin
2014-03-20 | E-GEOD-53600 | biostudies-arrayexpress
Project description:Small-cell lung carcinoma (SCLC) and large-cell neuroendocrine lung carcinoma (LCNEC) are high-grade lung neuroendocrine tumors (NET). However, comparative protein expression within SCLC and LCNEC remains unclear. Here, protein expression profiles were obtained via mass spectrometry-based proteomic analysis.
2019-05-14 | PXD013583 | JPOST Repository
Project description:Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine tumor with high mortality rates. Merkel cell polyomavirus (MCPyV), identified in the majority of MCC, may drive tumorigenesis via viral T antigens. However, mechanisms underlying pathogenesis in MCPyV-negative MCC remain poorly understood. To nominate genes contributing to pathogenesis of MCPyV-negative MCC, we performed DNA microarray analysis on 30 MCCs. MCPyV status of MCCs was determined by PCR for viral DNA and RNA. 1593 probe-sets were differentially expressed between MCPyV-negative and -positive MCC, with significant differential expression defined as at least 2-fold change in either direction and p-value of ≤ 0.05. MCPyV-negative tumors showed decreased RB1 expression, whereas MCPyV-positive tumors were enriched for immune response genes. Validation studies included immunohistochemistry demonstration of decreased RB protein expression in MCPyV-negative tumors and increased peritumoral CD8+ T lymphocytes surrounding MCPyV-positive tumors. In conclusion, our data suggest that loss of RB1 expression may play an important role in tumorigenesis of MCPyV-negative MCC. Functional and clinical validation studies are needed to determine whether this tumor suppressor pathway represents an avenue for targeted therapy. We used microarrays to characterize global gene expression patterns related to Merkel cell polyomavirus status in Merkel cell carcinoma. Furthermore, we compared Merkel cell carcinoma to less aggressive primary cutaneous carcinomas.
2012-10-18 | GSE39612 | GEO
Project description:When using cell lines to study cancer, phenotypic similarity to the original tumor is paramount. Yet, little has been done to characterize how closely Merkel cell carcinoma (MCC) cell lines model native tumors. To determine their similarity to MCC tumor samples, we characterized MCC cell lines via gene expression microarrays. Using whole transcriptome gene expression signatures and a computational bioinformatic approach, we identified significant differences between variant cell lines (UISO, MCC13, and MCC26) and fresh frozen MCC tumors. Conversely, the classic WaGa and Mkl-1 cell lines more closely represented the global transcriptome of MCC tumors. When compared to publicly available cancer lines, WaGa and Mkl-1 cells were similar to other neuroendocrine tumors, but the variant cell lines were not. WaGa and Mkl-1 cells grown as xenografts in mice had histological and immunophenotypical features consistent with MCC, while UISO xenograft tumors were atypical for MCC. Spectral karyotyping and short tandem repeat analysis of the UISO cells matched the original cell line's description, ruling out contamination. Our results validate the use of transcriptome analysis to assess the cancer cell line representativeness and indicate that UISO, MCC13, and MCC26 cell lines are not representative of MCC tumors, whereas WaGa and Mkl-1 more closely model MCC.
2014-12-23 | GSE50451 | GEO
Project description:We performed miRNA expression profiling in a series of human Merkel Cell carcinoma samples using a microarray approach. Significant differentially expressed miRNAs among groups were identified using SAM analysis. Agilent microarray platform containing 723 human miRNAs was used to determine miRNA expression profiles in 16 human Merkel cell carcinoma (MCC) samples. To validate the microarray platform, the expression levels of selected miRNAs were evaluated using qRT-PCR.
2013-12-31 | E-GEOD-43699 | biostudies-arrayexpress
Project description:Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin with growing incidence. In research immortalized cell lines are used for in vitro experiments in order to better understand the biology of this malignant disease.
2020-01-09 | PXD008181 | Pride
Project description:Merkel cells are epidermal mechanoreceptor cells responsible for the perception of gentle touch. Merkel cell carcinoma (MCC) is a rare and highly aggressive skin cancer. Although MCC histologically resembles Merkel cells, the cell of origin for MCC is unknown. MCC frequently contains integrated Merkel cell polyomavirus (MCPyV), a small DNA tumor virus with widespread prevalence. Whether MCPyV can transform Merkel cells is unknown. Here, we describe the isolation and long-term expansion of human Merkel cells from neonatal foreskin. We validated the expression of several Merkel cell-related factors by RNASeq, and assessed the ultrastructure by electron microscopy. Culture of Merkel cell preparations on an artificial basement membrane promoted the formation of structures containing both Merkel and non-Merkel cell populations. To determine whether Merkel cells were susceptible to transformation, we expressed tumor-derived MCPyV T antigens and additional oncogenes. We were unable to demonstrate tumorigenesis in immunodeficient mice, but were able to detect T antigen expression from excised cells weeks after implantation. These results highlight that foreskin-isolated Merkel cells can be propagated extensively, sustain expression of MCPyV T antigens, but are not susceptible to transformation by MCPyV, suggesting that Merkel cells from non-glabrous skin may not be a cell of origin for MCC.
2017-04-01 | GSE79657 | GEO
Project description:Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with neuroendocrine features. Although the role of epigenetic in tumorigenesis has been documented in most type of cancer, it is overlooked in MCC. The treatment options for MCC is limited and the five-year survival rate remains as low as 33%. In addition, recent studies have suggested multiple mechanisms of epigenetic dysregulation that may contribute to loss H3K27me3 and the tumorigenesis in MCC but not well studied. In this study, we conducted DNA methylation analysis of an existing retrospective cohort of clinically annotated MCC samples, which included samples from 8 primary tumors, three metastatic skin tumors, four metastatic lymph node tumors, and five paired normal tissue samples. Global DNA methylation profile was performed using Illumina Infinium MethylationEPIC array. Two MCC cell lines were also analyzed for DNA methylation and gene expression (RNA-seq) to confirm the correlation between DNA methylation and gene expression for MCC. Our analysis revealed 24,497 loci (14,456 genes) that showed significantly different DNA methylation pattern in the four groups (ANOVA p-value < 0.05 and standard deviation of mean of groups > 0.25) namely adjacent normal, primary tumor, metastatic skin, and metastatic lymph node in MCC patients. By GO terms analysis, the genes correlated with DNA methylation alteration associated with nervous system, cell adhesion, signal transduction, and development pathways. We also observed 870 probes differentially methylated in MCPyV positive and MCPyV negative tumor (FDR adjusted p-value < 0.05 and delta change greater than 0.4 or less than -0.4). Furthermore, using expression and DNA methylation data from two MCC cell lines (MS1 and MCC13) as validation, we identified 964 MCC specific genes directly regulated by DNA methylation either at promoter or gene body, which are highly enriched in nervous system related pathways. By this approach, we not only identify DNA methylation markers for MCC and MCPyV status but also genes regulated by DNA methylation in MCC, MCPyV status, and neuroendocrine features. Most importantly, our results may also suggest overexpression of KDM6B and EZHIP by loss of DNA methylation in their promoter may contribute to loss of H3K27me3 in MCC. In addition, we observed the DNA methylation profile of MS1 resembled MCC patient sample, while DNA methylation profile of MCC13 cell line was similar to small cell lung carcinoma (SCLC), which suggested that MCC13 cell line may originally come from SCLC. Taken together, we have demonstrated dramatic DNA methylation alteration along with four unique patterns in normal, primary and metastatic MCC. Our finding provides DNA methylation markers not only for diagnosis or prognosis of MCC and MCPyV status but also correlate gene expression status of MCC specific genes with important functional roles in MCC tumorigenesis, MCPyV expression, neuroendocrine feature and H3K27me3 status. The identification of DNA methylation alteration in MCC also provides foundation for potential implication of epigenetic therapy for MCC patients.
2021-07-13 | GSE160878 | GEO